Comparative genomics allows us to study the origin and evolution of gene families and to infer gene losses and gene gains that contributed to the morphological diversification and the functional innovations of different lineages of metazoans. Specifically, we have analyzed the origin and the evolution of genes and proteins that control the action of retinoic acid (RA), a small bio­active molecule related to important vertebrate- and chordate-specific functional fea­tures, such as axial patterning and the neural differentiation of the embryos. In the course of our studies, we have conducted comprehensive genomic analyses of the RA-signaling machinery in different lineages of metazoans, showing (i) the ancient origin of this machinery in metazoans, (ii) significant vertebrate-specific innovations in the control of retinoid homeostasis, (iii) an ancestral role of RA signaling in neuronal differentiation and neurite outgrowth, and (iv) independent losses of RA components during evolution, which may be related to changes in embryonic developmental modes and in expression patterns of the Hox clusters.

We have extended our com­parative genomic studies to other gene and protein families involved in significant signaling and phy­siological processes of metazoans. Actually, we have analyzed the evolution of com­ponents of the steroid-signaling pathway, the meta­bolism of nitric oxide, and the machinery of DNA methylation, among others. Our studies has opened new pers­pectives toward understanding how different sig­naling systems have been pre­served, lost and modified during the evolution of metazoans to suit the changing physiological and developmental requirements of these organisms.